X-31119880-G-GAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004006.3(DMD):c.*2038_*2039insTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0098 in 111,476 control chromosomes in the GnomAD database, including 9 homozygotes. There are 288 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (9 hom., 288 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: DMD NM_004006.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0850

Genes affected

DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-31119880-G-GAA is Benign according to our data. Variant chrX-31119880-G-GAA is described in ClinVar as [Likely_benign]. Clinvar id is 368202.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0098 (1093/111476) while in subpopulation AFR AF= 0.0339 (1041/30733). AF 95% confidence interval is 0.0322. There are 9 homozygotes in gnomad4. There are 288 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3	c.*2038_*2039insTT		3_prime_UTR_variant	79/79	ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9	c.*2038_*2039insTT		3_prime_UTR_variant	79/79	1	NM_004006.3	P4

Frequencies

GnomAD3 genomes AF: 0.00981 AC: 1093 AN: 111423 Hom.: 9 Cov.: 23 AF XY: 0.00852 AC XY: 287 AN XY: 33679

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00326

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.00664

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 294 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00980 AC: 1093 AN: 111476 Hom.: 9 Cov.: 23 AF XY: 0.00854 AC XY: 288 AN XY: 33742

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.00326

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000151

Gnomad4 OTH AF: 0.00656

Alfa AF: 0.00961 Hom.: 28

Bravo AF: 0.0118

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated cardiomyopathy 3B Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200703281; hg19: chrX-31137997;